Cortical anchoring of the microtubule cytoskeleton is essential for neuron polarity and functioning

Abstract

Neurons are among the most highly polarized cell types. They possess structurally and functionally different processes, axon and dendrites, to mediate information flow through the nervous system.Although it is well known that the microtubule cytoskeleton has a central role in establishing neuronal polarity, how its specific organization is established and maintained is little understood.Using the in vivo model system Caenorhabditis elegans, we found that the highly conserved UNC-119 protein provides a link between the membrane-associated Ankyrin (UNC-44) and the microtubuleassociated CRMP (UNC-33). Together they form a periodic membrane-associated complex that anchors axonal and dendritic microtubule bundles to the cell cortex. This anchoring is critical to maintain microtubule organization by opposing kinesin-1 powered microtubule sliding. Disturbing this molecular complex alters neuronal polarity and causes strong developmental defects of the nervous system leading to severely paralyzed animals.

Role of actin in organelle trafficking in neurons

“…Such early perturbations of F‐actin‐based structures, its effects on synapse dysfunction and contribution to neurodegeneration needs further investigation. Microtubule anchoring proteins like Ankyrin were also seen to have a periodic organization similar to actin‐spectrin based MPS (He et al, ; Xu et al, ). However, whether proteins like Ankyrin or microtubule anchoring itself is important for stabilizing the MPS is currently unknown.…”

“…Actin and associated proteins help the neurons withstand compressive forces and maintain neuronal structure through the formation of membrane associated periodic structures (MPS) (Hammarlund, Jorgensen, & Bastiani, 2007;Krieg, Dunn, & Goodman, 2014;Xu et al, 2013). MPS, is a quasione-dimensional periodic lattice structure present under the plasma membrane, comprising of braided ring like actin structures connected by αand β-spectrin heterotetramers (D'Este, Kamin, Gottfert, El-Hady, & Hell, 2015;He et al, 2019;Vassilopoulos, Gibaud, Jimenez, Caillol, & Leterrier, 2019;Zhong et al, 2014). Actin waves form growth-cone-like structures along the shaft of neuronal processes (Flynn, Pak, Shaw, Bradke, & Bamburg, 2009).…”

Casein Kinase 1δ Triggers Giant Ankyrin Expression

“…In the absence of giant Ankyrin, axons acquire dendritic characteristics like spines and post-synaptic densities (Hedstrom et al, 2008) and can exhibit branching patterns reminiscent of dendrites (Yamamoto et al, 2006), suggesting that Ankyrin is important for distinguishing the polarity of neurons with regards to axonal versus somatodendritic compartments. Finally, Ankyrin and beta-spectrin form a periodic membrane-associated cytoskeleton in the neurites of vertebrate and invertebrate neurons, including C. elegans neurons (He et al, 2019).…”